TFCP2 Is Required for YAP-Dependent Transcription to Stimulate Liver Malignancy.

Cell Reports
Xiao ZhangJiayi Wang

Abstract

Although YAP-dependent transcription is closely associated with liver tumorigenesis, the mechanism by which YAP maintains its function is poorly understood. Here, we show that TFCP2 is required for YAP-dependent transcription and liver malignancy. Mechanistically, YAP function is stimulated by TFCP2 via a WW-PSY interaction. TFCP2 also maintains YAP stability by inhibiting βTrCP. Notably, genomic co-occupancy of YAP and TFCP2 is revealed. TFCP2 acts as a transcription co-factor that stimulates YAP transcription by facilitating YAP binding with YAP binding motif (YBF)-containing transcription factors. Interestingly, TFCP2 also stimulated the YAP-TEAD interaction and TEAD target gene expression. Finally, several genes co-regulated by YAP and TFCP2 that contribute to YAP-dependent tumorigenesis are identified and verified. Thus, we establish a model showing that TFCP2 acts as a YAP co-factor to maintain YAP-dependent transcription in liver cancer cells, suggesting that simultaneous targeting of both YAP and TFCP2 may be an effective therapeutic approach.

Citations

Mar 19, 2019·Analytical Cellular Pathology (Amsterdam)·Hui DuYanfeng Xu
Dec 9, 2020·Critical Reviews in Oncology/hematology·Zahra Sadat RazaviHamed Mirzaei
Dec 30, 2020·Cancer Cell International·Yueyue YangJiayi Wang
Feb 15, 2021·Cellular and Molecular Life Sciences : CMLS·Lucy LeBlancJonghwan Kim
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Yong Suk Cho, Jin Jiang
Nov 13, 2021·Frontiers in Cell and Developmental Biology·Yikun WangXiao Zhang

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